AB1319 MUSCULOSKELETAL IMMUNE-RELATED ADVERSE EVENTS IN PATIENTS WITH SOLID CANCER TREATED WITH CHECKPOINT INHIBITORS: A CASE SERIES
Authors: A. Koltakova, A. Lila, M. Cherkasova, A. Fedenko
Journal: Annals of the Rheumatic Diseases (2022)

Background Immune-related adverse events (irAE) are common in cancer patients treated with checkpoint inhibitors. irAE can affect any organs and systems including musculoskeletal. The characteristics of immune-related musculoskeletal disorders (MD) still remain incomplete. Objectives to determine the characteristics of MD manifested during the treatment of solid cancer with check-point inhibitors in case series. Methods We identified 13 patients with inflammatory MD manifested during treatment with check-point inhibitors. Mean age of patients was 59±10 (ranged 43-74) years, 7 (54%) of them were female. Patients were treated with anti-PD-1 (77%) and anti-PD-L1 (33%) drugs (nivolumab [n=6], pembrolizumab [n=3], atezolizumab [n=3], prolgolimab [n=1]). Cancer types include melanoma (n=5), renal cell carcinoma (n=3), bladder cancer (n=2), non-small cell lung cancer (n=1), breast cancer (n=1), cervical cancer (n=1). 7 (54%) patients had another irAE also including thyroiditis (n=3), neuropathy (n=2), rash (n=1), sicca syndrome (n=1), hepatitis (n=1). The median time of musculoskeletal manifestation after the treatment`s onset was 20 [9-48] weeks. Results Musculoskeletal manifestations were performed by synovitis in 9 (69%) cases, tenosynovitis in 11 (85%), entesitis in 4 (31%), morning stiffness(&gt;30min) in 4 (31%). The most commonly affected areas were knees (77%) shoulders (69%), hands (69%) and feets (46%). Bilateral involvement was in 9 (69%) cases. MD was transient in 2 cases and persistent in 11 (9 patients with inflammatory arthritis and 2 patients with periarthritis). Clinical characteristic of inflammatory arthritis was represented by tenosynovitis more than synovitis in 3 cases (2 patients with symmetrical inflammatory polyarthritis and severe tenosynovitis, 1 patient with RS3PE-syndrome). In 6 cases inflammatory arthritis was represented by synovitis primarily (3 patients with symmetrical polyarthritis, 2 patients with oligoarthritis, 1 patient with monoarthritis). Severity of MD was assessed according to Common Terminology Criteria for Adverse Events V5.0. Grade 1 was in 2 cases (15.5%), grade 2 in 9 (69%), grade 3 in 2 (15.5%). Laboratory findings include ESR ≥30 mm/h in 7/12 (58%) cases (the median of ESR was 34 [14-42] mm/h); CRP &gt;5 mg/l in 7/10 (70%) cases (the median of CRP was 7.2 [4.6-12.9] mg/l). RF, ACPA were negative in all cases. ANA test was positive without any specificities in 7/10 (70%) cases in dilution 1:160 (n=2), 1:320 (n=3), 1:640 (n=2). Treatment of these conditions include NSAIDs (n=10), oral systemic corticosteroids (n=5), intra-articular corticosteroids (n=1), and csDMARDs (hydroxychloroquine [n=5] methotrexate [n=1]) as corticosteroid-sparing agents. 2 patients with polyarthritis and generalized tenosynovitis and 1 patient with symmetrical polyarthritis required treatment with ≤20 mg daily of prednisone. 2 patients with poly- and oligoarthritis were treated with 5-10 mg daily of prednisone. 5 patients with arthritis required long-term treatment with NSAIDs, corticosteroids and csDMARDs (the median of follow-up was 12 [3-12] months). 1 case of the inflammatory polyarthritis with severe tenosynovitis required to suspend the anticancer treatment with checkpoint inhibitor. Conclusion Our data demonstrated that the musculoskeletal irAE may be represented by heterogeneous manifestation and required long-term treatment. In rare cases musculoskeletal irAE can lead to suspension of the anticancer treatment with checkpoint inhibitors. Disclosure of Interests Anastasia Koltakova: None declared, Alexander Lila Speakers bureau: Pfizer Inc, MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB Inc, Maria Cherkasova: None declared, Aleksandr Fedenko: None declared